Molecular characterization of carbapenem-resistant Enterobacterales (CRE) and in vitro activity of novel beta lactams against CRE isolates from Malaysia.
Fairuz Abdul Rashid, Nurzam Suhaila Che Hussin, Nurul Fathiyah Zaipul Anuar, Noraziah Sahlan, Navindra Kumari Palanisamy, Fadzilah Mohd Nor
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引用次数: 0
Abstract
Knowledge gap on the susceptibility of novel β-lactam agents (cefiderocol, ceftazidime-avibactam, imipenem-cilastatin-relebectam, and aztreonam) against carbapenem-resistant Enterobacterales (CRE) has been recognized. This study aimed to genotypically characterize CRE isolates and investigate the novel β-lactam activity against CRE. CRE is defined as Enterobacterales that is phenotypically non-susceptible to any carbapenems, including imipenem, meropenem, and ertapenem. A total of 154 CRE isolates were collected from two tertiary centers in Malaysia from October 2023 to May 2024. Carbapenemase-producing genes (blaNDM, blaOXA-48, blaKPC, blaVIM, and blaIMP,) were detected using PCR. Susceptibility to β-lactams was determined using disc diffusion. Of 154 CRE isolates, 102 (66.2%) were carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE). blaNDM (76/102; 74.5%), blaOXA-48-like (17/102; 16.7%), blaNDM & blaOXA-48-like (8/102; 7.8%), and blaNDM & blaVIM (1/102; 1.0%) were identified among the CP-CRE isolates. The proportion of CRE isolates that exhibited susceptibility towards cefiderocol, ceftazidime-avibactam, and imipenem-cilastatin-relebactam was 86.4% (133/154), 41.6% (64/154), and 26.0% (40/154), respectively. Among blaNDM-harboring isolates, cefiderocol (57/76; 75.0%) demonstrated superior activity compared with ceftazidime-avibactam (3/76; 3.9%) and imipenem-cilastatin-relebectam (1/76; 1.3%). Among isolates harboring blaOXA-48-like, cefiderocol, ceftazidime-avibactam, and imipenem-cilastatin-relebectam demonstrated 100% (17/17), 70.6% (12/17), and 17.6% (3/17) susceptibility, respectively. Nine isolates that harbored two genes (eight blaNDM + blaOXA-48-like, one blaNDM + blaVIM) demonstrated 100% susceptibility to cefiderocol but 100% resistance to ceftazidime-avibactam and imipenem-cilastatin-relebectam. The ceftazidime-avibactam plus aztreonam combination achieved 100% susceptibility in isolates harboring metallo-β-lactamases-producing genes; blaNDM (76/76; 100%), blaNDM + blaOXA-48-like (8/8; 100%), and blaNDM + blaVIM (1/1; 100%). blaNDM was the most prevalent gene causing CRE. Cefiderocol has the greatest activity compared with other investigated β-lactams.IMPORTANCECarbapenem-resistant Enterobacterales (CRE) has been recognized as a priority and public health concern requiring urgent attention for the development of effective antimicrobial resistance (AMR) prevention and control strategies. Differentiating between carbapenemase-producing CRE (CP-CRE) and non-CP-CRE, along with identifying carbapenemase-producing genes, is essential for guiding targeted antibiotic therapy. Among novel β-lactam agents, cefiderocol and the combination of ceftazidime-avibactam and aztreonam have shown promising activity against blaNDM-producing CRE, supporting precision medicine approaches. Nevertheless, our study observed the emergence of cefiderocol resistance in isolates without prior drug exposure, highlighting a potential challenge in combating AMR.
期刊介绍：
Microbiology Spectrum publishes commissioned review articles on topics in microbiology representing ten content areas: Archaea; Food Microbiology; Bacterial Genetics, Cell Biology, and Physiology; Clinical Microbiology; Environmental Microbiology and Ecology; Eukaryotic Microbes; Genomics, Computational, and Synthetic Microbiology; Immunology; Pathogenesis; and Virology. Reviews are interrelated, with each review linking to other related content. A large board of Microbiology Spectrum editors aids in the development of topics for potential reviews and in the identification of an editor, or editors, who shepherd each collection.
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